Early fusion intermediate of ACE2-using coronavirus spike acting as an antiviral target

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2025-01-30 DOI:10.1016/j.cell.2025.01.012

Lixiao Xing, Zhimin Liu, Xinling Wang, Qianying Liu, Wei Xu, Qiyu Mao, Xiang Zhang, Aihua Hao, Shuai Xia, Zezhong Liu, Lujia Sun, Guangxu Zhang, Qian Wang, Zhenguo Chen, Shibo Jiang, Lei Sun, Lu Lu

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引用次数: 0

Abstract

Coronavirus fusion with and entry into the host cell depends on viral spike, which acts as a crucial component of viral infection. However, the lack of receptor-activated spike intermediate conformation has hindered a comprehensive understanding of spike-induced membrane fusion. Here, we captured an angiotensin-converting enzyme 2 (ACE2)-induced early fusion intermediate conformation (E-FIC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in which heptad repeat 1 (HR1) in S2 has ejected while S1 remains attached. This E-FIC can transition to the late FIC after S2′ cleavage. Leveraging this discovery, we designed an E-FIC-targeted dual-functional antiviral protein, AL5E. AL5E effectively inactivated ACE2-using coronaviruses and inhibited their infection, outperforming a mono-functional antiviral in protecting animals against these coronaviruses. This study has identified the E-FIC and used it as a target for the development of a dual-functional antiviral for the prevention and treatment of ACE2-using coronavirus infection.

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.